The eye and stem cells: the path to treating blindness

Last updated:
20 Aug 2012
The eye and stem cells: the path to treating blindness

Sight is arguably our most important sense; we rely upon it to navigate through our surroundings with ease. Loss of vision can have a huge impact on a person’s life, but many of the disorders that cause blindness are currently difficult or impossible to treat. Researchers are now using stem cell technology to explore possible new approaches to treatments for loss of vision.

Did you know?

Blinking damages the surface of your eyes, but you do it about 12 times per minute; it's a good job your eyes have stem cells to repair the damage!

Limbal stem cells from the human cornea, with a protein known as p63 stained yellow. Cell nuclei (which hold the DNA) are stained red.

Limbal stem cells from the human cornea, with a protein known as p63 stained yellow. Cell nuclei (which hold the DNA) are stained red.

Embryonic and induced pluripotent (iPS) stem cells cultured with growth factors become pigmented (brown in colour) and show characteristics of retinal pigment epithelium

Embryonic and induced pluripotent (iPS) stem cells cultured with growth factors become pigmented (brown in colour) and show characteristics of retinal pigment epithelium

Adding the right growth factors to Müller stem cells can make them become retinal nerve cells, as shown by the presence of a protein known as Islet 1 (pink).

Adding the right growth factors to Müller stem cells can make them become retinal nerve cells, as shown by the presence of a protein known as Islet 1 (pink).

Retinal nerve cells made from Müller stem cells (green) can move into the retinal nerve layers (blue) when transplanted into a rat eye with retinal damage.

Retinal nerve cells made from Müller stem cells (green) can move into the retinal nerve layers (blue) when transplanted into a rat eye with retinal damage.

About the eye

The eye is the organ responsible for our ability to see the world around us. It is able to detect light from the surrounding environment and transfer information about what it has detected to the brain. It is a very complex organ made up of multiple, specialized components, not unlike an electronic camera. The components, or tissues, are made up of many types of cells, each with a specific job to do to enable the tissues to perform specialized roles.

The eye: A complex organ made up of layers of different cell types.The eye: A complex organ made up of layers of different cell types.

The main parts of the eye are:

CorneaThe transparent ‘window’ on the front of the eye that allows the light to enter.
LensActs just like a lens in a camera by focusing the light that enters the eye.
RetinaThe electrical circuit at the back of the eye that is responsible for seeing. It is the most complex component of the eye and is made up of several different types of cells with specific roles. These include the photoreceptor cells, which detect the light entering the eye and produce an electrical signal.
Optic nerveA biological wire that connects the eye to the brain. It is responsible for transferring the electrical signal produced in the retina to the brain. The brain then interprets this signal to give us a picture of our environment. The optic nerve is closely associated with the retina.
Retinal pigment epitheliumA sheet of black cells that sit beneath the retina. This sheet supports the retina and has a number of important roles, including processing nutrients.

Disorders or diseases of the eye occur when one or more of these components is damaged, and/or stops working properly. Different disorders develop depending upon which component(s) are not working. The difficulty in treating these problems is that, unlike the electronic parts of a camera, new biological components for the eye are not easy to obtain. This is where stem cell technology may be of use. Stem cells can act as a source of new, healthy specialized cells and may provide a way to replace damaged cells in the eye. There are several types of stem cells that could be used in different ways, depending upon the particular disorder to be treated. So what is current research focused on?

Repairing the cornea - limbal stem cells

Cells that make up the cornea (the window part of the eye) are constantly damaged by blinking and exposure to the outside world. To repair this damage, we have a small number of stem cells at the edge of the cornea, known as limbal stem cells. They are responsible for making new corneal cells to replace damaged ones. If these stem cells are lost due to injury or disease, the cornea can no longer be repaired. This affects the ability of light to enter the eye, resulting in a significant loss of vision.

Transplantation of limbal stem cells from a healthy eye can repair the cornea and give the patient back their sight. However, this procedure carries some risks to the healthy donor eye and to the patient, and other problems mean the approach isn’t ideal. For example, if a patient has damage to both of their eyes, it may not be possible to obtain any limbal stem cells. Cells from a donor can be used, but donors are in short supply, success rates are lower, and donor cells are usually only effective in the short to medium term.

Repairing the cornea: Currently the only stem-cell-based therapy for the eye that has been proven to work in clinical trials.Repairing the cornea: Currently the only stem-cell-based therapy for the eye that has been proven to work in clinical trials.

At present, this is the only available stem cell treatment in the eye that has been proven by to work. It is not yet widely available; further clinical studies with larger numbers of patients must now be carried out before this therapy can be approved by regulatory authorities for widespread use in Europe.

Recent research has led to improvements in methods for growing limbal stem cells in the lab, and to better transplantation techniques. However, there are still limitations in the amount of new cells that can be obtained from a sample taken from the eye. Researchers are currently investigating the possibility of using a different approach – starting from embryonic stem cells or induced pluripotent stem (iPS) cells  to make new limbal stem cells in the lab. This would remove the need for complex surgery for donors, as well as providing a theoretically endless source of large quantities of limbal stem cells for patients who require new ones. It is hoped that this kind of approach will be available for patients in the future.


Developing treatments for retinal diseases

Replacing retinal pigment epithelial cells
Retinal pigment epithelial (RPE) cells have a number of important jobs, including looking after the adjacent retina. If these cells stop working properly due to damage or disease, then certain parts of the retina die. As the retina is the component of the eye responsible for detecting light, this leads to the onset of blindness. RPE cells can be damaged in a variety of diseases such as: age-related macular degeneration (AMD), retinitis pigmentosa and Leber’s congenital aneurosis.

One way to treat these diseases would be to replace the damaged RPE cells with transplanted healthy cells. Unfortunately, it is not possible to take healthy RPE cells from donors so it is necessary to find another source of cells for transplantation. Scientists have recently produced new RPE cells from both embryonic stem cells and iPS cells in the lab. The safety of embryonic stem cell-derived RPE cells is currently being tested in a clinical trial for patients with Stargardt’s macular dystrophy, and it is hoped that a similar trial will follow for patients suffering from age-related macular degeneration (AMD).

Replacement of damaged RPE cells will only be effective in patients who still have at least part of a working retina, and therefore some level of vision (i.e. at early stages of the disease). This is because the RPE cells are not themselves responsible for ‘seeing’, but are actually responsible for supporting the ‘seeing’ retina. Sight is lost in these types of diseases when the retina begins to degenerate because the RPE cells are not doing their job properly. So the RPE cells need to be replaced in time for them to support a retina that is still working. It is hoped that transplantation of new RPE cells will then permanently halt further loss of vision, and in some cases may even improve vision to some degree.

Replacing retinal pigment epithelial cells: Techniques for growing cells for therapies are being researched and tested in early clinical safety trials.Replacing retinal pigment epithelial cells: Techniques for growing cells for therapies are being researched and tested in early clinical safety trials.

Replacing retinal cells
In many of the cases where vision is lost, we often find that the problem lies with malfunctioning retinal circuitry. Different disorders occur when particular, specialized cells in the circuit either stop working properly or die off. Despite the retina being more complicated than other components of the eye, it is hoped that if a source of new retinal cells can be found, we may be able to replace the damaged or dying cells to repair the retina. In addition, this approach may also help to repair damage caused to the optic nerve.

Again, scientists have turned to stem cell technology to provide the source of replacement cells. Several studies have now reported that both embryonic stem cells and iPS cells can be turned into different types of retinal cells in the lab. Within the eye, a type of cell called the Müller cell, which is found in the retina, is known to act as a stem cell in some species, such as the zebra fish. It has been suggested that this cell may also be able to act as a stem cell in humans, in which case it may provide another source of retinal cells for repair of the retina.

Unlike RPE cell transplantation, direct repair of the retina may allow patients who have already lost their vision to have it restored to some degree. This gives hope for patients with disorders like late-stage age-related macular degeneration, where the light-sensitive photoreceptor cells in the retina have already been lost. This type of research may also provide new treatments for people who suffer from retinal diseases like retinitis pigmentosa and glaucoma. However, despite encouraging evidence, such research is very much in its infancy. There are currently no patient clinical trials planned using this type of approach, as significant further research is still required first.

Replacing the nerve cells of the retina: Current research aims to understand how to produce retinal nerve cells that could be used in future therapies.Replacing the nerve cells of the retina: Current research aims to understand how to produce retinal nerve cells that could be used in future therapies.

The future

Stem cell technology holds great potential for improving the lives of people who suffer from visual disorders. A number of studies are currently being undertaken in order to develop new therapies to treat, and/or prevent a loss of vision. Central to this research is the development of our understanding of how different types of stem cells behave, and how best to harness their potential in the eye. A tailored approach is required, dependent upon the particular problem a patient is experiencing. Stem cells are not a one-stop, generic cure, but they do hold exciting potential for the production of new biological components that can be used to repair the eye.

Find out more

Interview with Prof Pete Coffey on a stem cell trial for macular degeneration (February 2014)
Patient information from the London Project to Cure Blindness
A review of recent clinical trials of stem cells in the eye
EuroStemCell Clinical Trials Update January 2012
Stem Cell Revolutions - a documentary with a chapter on macular degeneration
News report about research into potential treatment of glaucoma
EuroStemCell update on OptiStem – a research project carrying out work on the cornea
The European Blind Union
Royal National Institute of Blind People, UK

Acknowledgements and references

This factsheet was created by G. Astrid Limb, Silke Becker and Matt Smart. Fact sheet reviewed by Pete Coffey with input on information about repair of the cornea from Michele de Luca.

Images of limbal epithelial stem cells and picture showing the use of embryonic/iPS cells by Dr Hannah Levis and Dr Amanda Carr, respectively, UCL Institute of Ophthalmology. All other images from the laboratory of Astrid Limb.